Opioid antagonism modulates wanting-related frontostriatal connectivity
- Department of Psychology, Ludwig Maximilian University, Germany
- Zurich Center for Neuroeconomics, Department of Economics, University of Zurich, Switzerland
- Department of Neurology, Northwestern University Feinberg School of Medicine, United States
- Experimental and Clinical Pharmacopsychology, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland
- Neuroscience Center Zurich, University of Zurich and Swiss Federal Institute of Technology Zurich, Switzerland
Figures
Figure 1
Task procedure and behavioral results.
(A) Participants rated in the MRI scanner how much they wanted or liked objects before (pre-test) or after (post-test) they won or lost these items in a game between the scanning sessions. (B) On each trial, a cue indicated whether a wanting or liking rating was required, followed by the presentation of the current object (here: a pick-up sticks game). Participants had to rate how much they wanted or liked the presented object within 3.5 s, then the next trial started after a variable inter-trial interval (mean = 3 s). (C) Liking ratings were significantly reduced for objects that were lost relative to won in the gamble, while wanting ratings did not significantly differ between lost versus won items. (D) The opioid antagonist naltrexone significantly reduced wanting ratings relative to placebo, while liking ratings were unaffected by naltrexone or the dopamine antagonist amisulpride. For illustration purposes, participant-specific mean wanting/liking ratings are plotted on a scale from 0 to 10, while the statistical analyses are conducted on the participant- and item-specific wanting and liking ratings. Error bars indicate standard error of the mean, black dots represent individual data points. *p < 0.05, ***p < 0.001.
Figure 2
Neural correlates of (A) wanting and (B) liking independently of behavioral relevance.
Wanting correlated with activation in dorsolateral prefrontal cortex (DLPFC), ventromedial prefrontal cortex (VMPFC), and posterior cingulate cortex (PCC) (whole-brain FWE-corrected). Liking correlated with activation in dorsal PCC (whole-brain FWE-corrected) and orbitofrontal cortex (small-volume FWE-corrected). (C) Wanting ratings significantly correlated with activation in the striatum during wanting judgements (small-volume FWE-corrected). Images are thresholded at p < 0.001 uncorrected.
Figure 3
Effects of Judgement type and drug on parametric striatal connectivity.
(A) On wanting trials (collapsed across drug groups), dorsolateral prefrontal cortex (DLPFC)-striatum connectivity was enhanced for wanting relative to liking aspects of rewards (image thresholded at p < 0.001 uncorrected). (B) Wanting-related DLPFC-striatum coupling was significantly stronger under naltrexone compared with placebo (image thresholded at p < 0.001 uncorrected). (C, D) Extracted parameter estimates for DLPFC (as defined by the significant cluster in general linear model 1 [GLM-1]), separately for wanting and liking judgements. (C) If wanting judgements were behaviorally relevant, naltrexone increased wanting relative to liking-related DLPFC-striatum connectivity. (D) No significant drug effects on DLPFC-striatum connectivity were observed on liking trials. Error bars indicate standard error of the mean, black dots represent individual data points. *p < 0.05.
Tables
Table 1
Results of mixed general linear model 1 (MGLM-1) on wanting and liking ratings in the post-test as function of Judgement (wanting versus liking), Item type (lost versus won), and Pre-test ratings.
Standard errors of the mean (SE) are in brackets.
| Beta (SE) | t-Value | df | p-Value | |
|---|---|---|---|---|
| Intercept | 0.21 (0.66) | 0.32 | 119 | 0.75 |
| Judgement | –2.27 (0.64) | 3.54 | 125 | <0.001 |
| Item type | 0.07 (1.10) | 0.07 | 98 | 0.95 |
| Pre-test | 79.87 (0.50) | 158.30 | 124 | <0.001 |
| Judgement × Item type | 2.01 (1.24) | 1.62 | 109 | 0.11 |
| Judgement × Pre-test | 2.41 (0.61) | 3.93 | 289 | <0.001 |
| Item type × Pre-test | –1.62 (0.71) | 2.26 | 133 | 0.03 |
| Judgement × Item type × Pre-test | 0.91 (0.90) | 1.01 | 288 | 0.31 |
Table 2
Results for mixed general linear model 2 (MGLM-2) assessing drug effects on wanting and liking ratings as function of Drug (amisulpride versus placebo and naltrexone versus placebo), Judgement (wanting versus liking), and Session (pre-test versus post-test).
Standard errors of the mean (SE) are in brackets.
| Beta (SE) | t-Value | df | p-Value | |
|---|---|---|---|---|
| Intercept | 3.62 (5.50) | 0.66 | 98 | 0.51 |
| Amisulpride | 2.37 (5.09) | 0.47 | 114 | 0.64 |
| Naltrexone | –6.80 (5.19) | 1.31 | 114 | 0.19 |
| Judgement | 4.38 (2.08) | 2.11 | 125 | 0.04 |
| Session | –3.30 (1.98) | 1.67 | 1612 | 0.10 |
| Amisulpride × Judgement | 3.79 (2.92) | 1.30 | 126 | 0.20 |
| Naltrexone × Judgement | 7.02 (2.98) | 2.36 | 125 | 0.02 |
| Amisulpride × Session | 0.02 (2.79) | 0.00 | 1629 | 0.99 |
| Naltrexone × Session | 2.70 (2.84) | 0.95 | 1618 | 0.34 |
| Judgement × Session | –1.09 (1.97) | 0.55 | 1845 | 0.58 |
| Amisulpride × Judgement × Session | –1.50 (2.78) | 0.54 | 1856 | 0.59 |
| Naltrexone × Judgement × Session | –2.95 (2.83) | 1.04 | 1853 | 0.30 |
Table 3
Anatomical locations and MNI coordinates of the peak activations correlating with wanting ratings in general linear model 1 (GLM-1).
We report activations surviving whole-brain FWE correction at peak level (p < 0.05). Hem = Hemisphere (L = left, R = right); BA = Brodmann area.
| MNI coordinates | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Region | Hem | BA | X | Y | Z | k | Z | |||||
| VMPFC | R/L | 10 | 0 | 44 | –7 | 439 | 7.32 | |||||
| DLPFC | L | 8 | –21 | 38 | 44 | 39 | 6.63 | |||||
| L | 8 | –33 | 23 | 44 | 4 | 5.11 | ||||||
| PCC | L | 23 | -3 | –37 | 38 | 39 | 5.29 | |||||
| R/L | 23 | 0 | –13 | 35 | 1 | 4.79 | ||||||
| Anterior cingulate cortex | R | 32 | 6 | 35 | 11 | 3 | 5.27 | |||||
| Frontopolar cortex | L | 10 | –12 | 65 | 20 | 1 | 4.82 | |||||
Table 4
Anatomical locations and MNI coordinates of the peak activations correlating with liking ratings in general linear model 1 (GLM-1).
We report activations surviving whole-brain FWE correction at peak level (p < 0.05). Hem = Hemisphere (L = left, R = right); BA = Brodmann area.
| MNI coordinates | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Region | Hem | BA | X | Y | Z | k | Z | |||||
| Dorsal PCC | L | 31 | –9 | –64 | 38 | 1 | 4.87 | |||||
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Opioid antagonism modulates wanting-related frontostriatal connectivity
eLife 10:e71077.
https://doi.org/10.7554/eLife.71077
